Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes

\ua9 The Author(s) 2024.Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases

Trait emotional intelligence, mood states & cortisol response to a treadmill ultramarathon

INTRODUCTION: Ultramarathon competitors experience & have to manage & overcome a complexity of physiological & psychological stresses. Trait emotional intelligence (TEI) is an individual’s perception & understanding of how their emotions impact their thoughts & behaviours during competition & plays an important role in their ability to employ strategies to regulate them. The aim of this study was to investigate TEI & its effect on performance, mood states & serum cortisol levels over an 80.5km treadmill ultramarathon. METHODS: Twelve ultramarathon runners completed an 80.5km time-trial on a treadmill & were instructed to cover the distance in the fastest possible time. Runner TEI was measured using the 33-item emotional intelligence scale (Schutte et al., 1998) prior to the trial. A mood state questionnaire (BRUMS: Terry et al., 2003) was completed prior (baseline), immediately before (pre), at 40.25km (halfway) & on completion of 80.5km (post), as were serum cortisol concentrations, measured by competitive ELISA-type electrochemiluminescence assay. RESULTS: Average completion time was 09:00:18±01:14:07 (hh:mm:ss), at a running velocity of 9.8±1.3km.h-1. Increases in serum cortisol were observed between pre & halfway, & between halfway & post time points (p=0.001 & p=0.003, respectively). Significant decreases were observed between both baseline & pre time points compared to the post time point for ‘Vigor’ (p=0.015 & p=0.01, respectively). Significant increases were also identified for ‘Fatigue’ between pre & halfway, &, pre & post (p=0.05 & p0.001). Significantly higher total mood disturbance (TMD) was also observed between baseline & post, as well as between pre & post time points (p=0.001). CONCLUSION: The findings of the current study highlight the complex interactions of both physiological & psychological stresses imposed by an ultramarathon, demonstrated by the expected increase in fatigue & decrease in vigor over the course of the ultramarathon. Participants with a higher TEI displayed greater post-trial cortisol responses which may suggest that they are more aware of their emotions during an ultramarathon. These findings may give insight into what draws individuals to the sport of ultramarathon running, help to identify the stressors they face & further help develop strategies to aid both completion & performance in ultramarathon events. REFERENCES Schutte, N. S., Malouff, J. M., Hall, L. E., Haggerty, D. J., Cooper, J. T., Golden, C. J., Dornheim, L. (1998). Pers Indiv Differ,25:167–77. Terry P.C., Lane A.M., Fogarty G.J. (2003). Psych Sport Ex,44:125-139